Stephan A. Grupp, MD, PhD

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Stephan A. Grupp, MD, PhD, is Section Chief of the Cellular Therapy and Transplant Section, Director of the Cancer Immunotherapy Program, and Medical Director of the Cell and Gene Therapy Laboratory. He holds the Yetta Deitch Novotny Endowed Chair in Pediatric Oncology.

Areas of Expertise: Development of engineered T cell therapies such as CTL019, Novel leukemia therapy, Stem cell transplants, Treatment of high-risk neuroblastoma
Locations: Main Hospital

Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

As an attending physician in the Cancer Center, Section Chief of the Cellular Therapy and Transplant Section, Director of the Cancer Immunotherapy Program, and the Medical Director of the Cell and Gene Therapy Laboratory, I take on many roles here at CHOP. But in each of them, I’m a pediatric oncologist working to improve outcomes for children battling difficult cancers. I received an M.D. and Ph.D. from the University of Cincinnati College of Medicine and completed residency and fellowships at Harvard Medical School, Boston Children’s Hospital, Dana Farber Cancer Institute and Brigham and Women’s Hospital, before coming to CHOP in 1996.

T cells have the potential to kill cancer cells, but in patients with cancer, they’re not doing that job. By genetically modifying them, we can make the cells behave differently so they’ll attack cancer cells, using an engineered targeting protein called a chimeric antigen receptor (CAR). Working with our colleagues at the University of Pennsylvania and later with Novartis, we have developed CAR T therapy for children with ALL, opening up a brand new field of medicine and resulting in the first global approval of an engineered cell therapy and also the first gene therapy approved in the US. During the development of this product, I was honored to run the initial CHOP phase 1 trial, the first US multicenter trial of a CAR T therapy, the first international trial (sponsored by Novartis), and the first CAR T pivotal trial. This work has now been extended to using these genetically modified CAR T cells to treat patients with other B cell cancers such as B cell non-Hodgkin lymphoma (NHL), the adult disease chronic lymphocytic leukemia, and other B cell malignancies. In addition to FDA and global health authority approvals, this work has received international attention, generating dozens of high impact scientific publications, including three in the New England Journal of Medicine.

Exciting trials just opening or in the immediate CHOP cell therapy pipeline will extend these results to AML, new forms of ALL, and (coming soon) pediatric solid tumors, providing options for patients with no other therapies available.

Using similar approaches, and working with our colleagues in the Division of Hematology and the CuRED program, we now have multiple clinical trials testing ways to genetically modify bone marrow stem cells to cure diseases like sickle cell anemia and thalassemia. Over 100,000 patients in the US suffer from these red blood cell disorders. This illustrates the commitment of the CTTS to cure patients with cell therapy that have life-threatening, but non-cancer, diseases. Over the past 20 years, our Transplant group has evolved to the point where half the transplants we do are for non-cancer diagnoses.

In one of my clinical roles, I also work with patients with the most aggressive form of neuroblastoma, a difficult-to-treat childhood cancer that begins in the peripheral (non-brain) nerve tissue of infants and young children. I work alongside a world-class team of physicians and multi-disciplinary specialists who are dedicated to treating this disease. The tandem transplant approach that is now standard of care across the country was developed by our group here at CHOP. In addition, the neuroblastoma team at CHOP does studies of the patient’s genetics and the unique characteristics of their disease to offer a personalized treatment approach. We also were part of the group that did the nationwide clinical trial establishing antibody-based immunotherapy as the new standard of care in neuroblastoma.

In the lab and the hospital, I am a lab scientist, a cell therapist, and a stem cell transplanter. In the Cell and Gene Therapy Laboratory, we collect cells for transplant and CAR T therapy and manage cell processing: both collecting the original cells and engineering the cells so the right cell type gets into the patient.

What first brought me to CHOP was the opportunity to conduct transplant and leukemia research, and work in CHOP’s intensely translational environment. Today, I run a lab where the research is devoted to developing cell-based and molecularly-targeted therapies to treat leukemia and solid tumors. The goal of all the work I do is to improve treatment options for children with cancer, not just at CHOP but throughout the world. Whether that’s accomplished by offering alternative therapies that are less toxic than today’s standards of care, advanced treatments for high-risk disease that fight cancer in new and different ways, or cures for genetic disorders like sickle cell, if we impact the standard of care I consider that a success.

Education and Training

Medical School

MD - University of Cincinnati College of Medicine MD, Cincinnati, OH

Internship

Pediatrics - Children's Hospital, Boston, MA

Residency

Pediatrics - Children's Hospital Fellowships

Pediatrics - Children's Hospital, Boston, MA

Fellowship

Pediatrics - Harvard Medical School, Boston, MA
Pediatric Hematology/Oncology - Dana Farber Cancer Institute and Children's Hospital, Boston, MA
Research Fellow in Immunology - Brigham and Women's Hospital, Boston, MA

Board Certification

Pediatric Hematology-Oncology
Pediatrics

Graduate Degree

PhD - University of Cincinnati College of Medicine PhD, Cincinnati, OH

Titles and Academic Titles

Chief, Cellular Therapy and Transplant Section

Director, Cancer Immunotherapy Program

Attending Physician, Division of Oncology

Medical Director, Cell and Gene Therapy Laboratory

Principal Investigator

Co-lead, Pediatric Oncology, Abramson Cancer Center

Yetta Deitch Novotny Endowed Chair in Pediatric Oncology

Novotny Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Departments and Services

Areas of Focus

Laboratories & Research Programs

Research Interests

engineered T cell and stem cell therapies

novel leukemia therapy

CAR T Development Core (with David Barrett, MD)

Children's Hospital of Philadelphia Research Institute summary

Publications

Papers

2020

Singh N, Lee YG, Shestova O, Ravikumar P, Hayer KE, Hong SJ, Lu XM, Pajarillo R, Agarwal S, Kuramitsu S, Orlando EJ, Mueller KT, Good CR, Berger SL, Shalem O, Weitzman MD, Frey NV, Maude SL, Grupp SA, June CH, Gill S, Ruella M. 2020. Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction. Cancer Discovery 10(4):552-567. April 2020. PMID: 32001516.

Kadauke, S, RM Myers, Y Li, R Aplenc, D Baniewicz, DM Barrett, AB Leahy, C Callahan, JG Dolan, JC Fitzgerald, W Gladney, SF Lacey, H Liu, SL Maude, R McGuire, LS Motley, DT Teachey, G Wertheim, L Wray, AM DiNofia, SA Grupp. 2020. Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome after CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial. J Clin Oncol, in press.

Maus, MV, S Alexander, MR Bishop, JN Brudno, C Callahan, ML Davila, C Diamonte, J Dietrich, JC Fitzgerald, MJ Frigault, TJ Fry, JL Holter-Chakrabarty, KV Komanduri, DW Lee, FL Locke, SL Maude, PL McCarthy, E Mead, SS Neelapu, TG Neilan, BD Santomasso, EJ Shpall, DT Teachey, CJ Turtle, T Whitehead, SA Grupp. 2020. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunotherapy Cancer, in press.

2019

Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. 2019. Effect of tandem autologous stem cell transplant vs single transplant on event-free survival in patients with high-risk neuroblastoma: A randomized clinical trial. JAMA 322 (8): 746-755. August 27, 2019. PMID: 31454045. PMCID: PMC6714031.

Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. 2019. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 20 (12): 1710-1718. December 2019. PMID: 31606419.

2018

Maude, SL, TW Laetsch, J Buechner, S Rives, M Boyer, H Bittencourt, P Bader, MR Verneris, HE Stefanski, GD Myers, M Qayed, B De Moerloose, H Hiramatsu, K Schlis, KL Davis, PL Martin, ER Nemecek, GA Yanik, C Peters, A Baruchel, N Boissel, F Mechinaud, A Balduzzi, J Krueger, CH June, BL Levine, P Wood, T Taran, M Leung, KT Mueller, Y Zhang, K Sen, D Lebwohl, MA Pulsipher, and SA Grupp. 2018. Tisagenlecleucel in Children and Young Adults with B Lymphoblastic Leukemia. New England Journal of Medicine. 378(5):439-448. PMID: 29385370.

Teachey DT, Bishop MR, Maloney DG, Grupp SA. 2018. Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'. Nature Reviews Clinical Oncology. April. 15(4):218. PMID: 29434335.

Ruella, M,  J Xu, DM Barrett, JA Fraietta, TJ Reich, DE Ambrose, M Klichinsky, O Shestova, PR Patel, I Kulikovskaya, F Nazimuddin, VG Bhoj, EJ Orlando, TJ Fry, H Bitter, SL Maude, BL Levine, CL Nobles, FD Bushman, RM Young, J Scholler, SI Gill, CH June, SA Grupp, SF Lacey and JJ Melenhorst. October 2018. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. **Nature Medicine 24(10): 1499-1503. PMID 30275568.

*Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, De Moerloose B, Nemecek ER, Bittencourt H, Hiramatsu H, Buechner J, Davies SM, Verneris MR, Nguyen K, Brogdon JL, Bitter H, Morrissey M, Pierog P, Pantano S, Engelman JA, Winckler W. October 2018. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.
**Nature Medicine 24(10): 1504-1506. PMID 30275569.
**same issue

Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. 2018. ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant 25(4): 625-638. PMID 30592986.

2017

Bagatell R, Grupp SA. Refining megatherapy, improving outcome in neuroblastoma. Lancet Oncol. 2017 Apr;18(4):423-424. PMID: 28259607.

Bride, KL, T Vincent, K Smith-Whitley, MP Lambert, JJ. Bleesing, AE Seif, CS Manno, J Casper, SA Grupp, and DT Teachey. 2016. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 127:17-28. PMID: 26504182, PMCID: PMC4705607.
*Blood Plenary Paper

Singh, N, J Perazzelli, SA Grupp, DM Barrett. 2016. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci. Transl. Med. 8, 320ra3. PMID: 26738796.

Teachey, DT, SF Lacey, PA Shaw, JJ Melenhorst, SL Maude, NV Frey, E Pequignot, VE Gonzalez, F Chen, J Finklestein, DM Barrett, SL Weiss, JC Fitzgerald, RA Berg, R Aplenc, C Callahan, SR Rheingold, Z Zheng, S Rose-John, JC White, F Nazimuddin, G Wertheim, BL Levine, CH June, DL Porter, and SA Grupp. 2016. Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T cell Therapy for Acute Lymphoblastic Leukemia. Cancer Discovery 6(6):664-79. PMID: 27076371. PMCID: PMC5448406.

2016

Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J, Lacey SF, Melenhorst JJ, Morrissette JJ, Christian DA, Hunter CA, Kalos M, Porter DL, June CH, Grupp SA, Gill S. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016 Oct 3;126(10):3814-3826. PMID: 27571406; PMCID: PMC5096828.

Porter, DL, WT Hwang, NV Frey, SF Lacey, PA Shaw, AW Loren, A Bagg, KT Marcucci, A Shen, V Gonzalez, D Ambrose, SA Grupp, A Chew, Z Zheng, MC Milone, BL Levine, JJ Melenhorst, CH June. 2015. Chimeric Antigen Receptor T Cells Persist and Induce Sustained Remissions in Relapsed Refractory Chronic Lymphocytic Leukemia. Science Translational Medicine. 7:303ra139. PMID: 26333935.

Singh N, Kulikovskaya I, Barrett DM, Binder-Scholl G, Jakobsen B, Martinez D, Pawel B, June CH, Kalos MD, Grupp SA. 2015. T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma. Oncoimmunology. 5(1):e1040216. PMID: 26942053 PMCID: PMC4760344.

2015

Sotillo, E, DM Barrett, KL Black, A Bagashev, D Oldridge, G Wu, R Sussman, C Lanauze, M Ruella, MR Gazzara, NM Martinez, CT Harrington, EY Chung, J Perazzelli, TJ Hofmann, SL Maude, P Raman, A Barrera, S Gill, SF Lacey, JJ Melenhorst, D Allman, E Jacoby, T Fry, C Mackall, Y Barash, KW Lynch, JM Maris, SA Grupp, and A Thomas-Tikhonenko. 2015. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discovery 5(12):1282-95. PMID: 26516065, PMCID: PMC4670800.

2014

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. PMID: 25317870; PMCID: PMC4267531.

2013

Grupp, SA, M Kalos, D Barrett, R Aplenc, DL Porter, SR Rheingold, DT Teachey, BL Levine, and CH June. 2013. Induction of complete remissions of ALL by chimeric antigen receptor-expressing T cells. New England Journal of Medicine. 368(16):1509-18. PMID: 23527958;  PMCID: 4058440; NIHMS: 474709.

Kreissman, SG, RC Seeger, KK Matthay, WB London, R Sposto, SA Grupp, DA Haas-Kogan, MP LaQuaglia, AL Yu, L Diller, A Buxton, JR Park, SL Cohn, JM Maris, CP Reynolds, and JG Villablanca. 2013. Prospective, Randomized Trial of Purged versus Non-Purged Peripheral Blood Stem Cell Transplant for High Risk Neuroblastoma. Lancet Oncology, 14(10):999-1008.  PMID: 23890779 ; PMCID: 3963485; NIHMS: 540046.

Teachey, DT, SR Rheingold, SL Maude, G Zugmaier, DM Barrett, AE Seif, KE Nichols, EK Suppa, M Kalos, RA Berg, JC Fitzgerald, R Aplenc, L Gore, and SA Grupp. 2013. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 121(26):5154-5157. PMID: 23678006. NIHMS: 607684.  PMCID: 4123427.

Awards and Honors

2019, Daniel Drake Mefal, University of Cincinnati College of Medicine

2019, Elected to the National Academy of Medicine (NAM)

2018, William Osler Patient Oriented Research Award, Penn Medicine

2016, Scientist of the Year, Philly Geek Awards, Technical.ly

2015, Fred Saunders Lectureship and Award, Canadian Blood and Marrow Transplant Society

2015, Oski Lectureship and Award, American Society of Pediatric Hematology/Oncology

2014, Audrey Evans Service Award, Ronald McDonald House Charities

2014, van Bekkum Prize, European Bone Marrow Transplantation Society

2014, Clinical Research Forum Herbert Pardes First Place Achievement Award

2014, Clinical Research Forum Top 10 Clinical Research US Achievement Award

2014, Pennsylvania Bio Patient Impact Award

2013, Visiting Professor, Stanford University, Stanford, CA

2013, Chai Lifeline Community Service Award

2012, Yetta Deitch Novotny Chair, CHOP

2011-2014, Elected to the ASPHO Board of Trustees

2010, Elected to American Pediatric Society

2009, Transplantation Visiting Professor, Hospital for Sick Children and University of Toronto, Toronto, Canada

2008, W.E. Hathaway Visiting Professor, University of Colorado, Denver, CO

2008, Aflac Visiting Professor, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA

2007, Eagles Fly for Leukemia 2007 Lifetime Achievement Award

2003, Elected to the Society for Pediatric Research

2002, Research Recognition Award, Leukemia and Lymphoma Society, Philadelphia, Pennsylvania

2000-2005, Stanford Young Investigator in Molecular Oncology

1997, 1997 Research Award, 5th International Meeting on Blood Cell Transplantation, Omaha, Nebraska

1993-1996, 1993-96 Amy C. Potter Fellow

1987, Bogen Award for Outstanding Medical Student Research, University of Cincinnati College of Medicine

1986, Research Award, Midwest Medical Research Forum, University of Michigan

1981, Graduated Magna cum Laude - University of Cincinnati, Cincinnati, OH